The goals of this project is to determine how HIV-1 alters the behavior of host cells. Infected patients suffer recurrent infections due to reduced CD4+ T cells, Kaposi's sarcoma, B-cell lymphomas and neurological changes. We find that CD4+ T cells infected with the HIV-1 are several-fold more adhesive to fibronectin undergo spreading with increased expression of cell surface filopodia. The interaction with fibronectin is mediated by the alpha-5-beta1 integrin. We likewise find that tat protein is biologically active with neural cells, but the cellular receptor does not appear to be an integrin. Renal disease is common in AIDS patients and in mice made transgenic with the tat gene. We are investigating the regulation of extracellular matrix gene expression in the kidney of such transgenic mice. Our goal is to obtain a better understanding of the mechanisms involved in the pathology of this virus infection.